T9185C

# **General Information**

| **Position** | **9185** | **Variant** | **m.9185T\>C** | **Locus** | **MT\-ATP6** | **Amino\-AcidChange** | **L220P** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-pathogenic | **Pathogenicity** | Cfrm \[P] |

"Pathogenicity" status is derived from published literature or predictions from bioinformatics tools. Researchers and clinicians are cautioned that additional data and/or analysis may still be necessary to confirm the pathological significance of these variants. For more information, please see [Mitofam Info](https://mitofam.com/doc/385/).

# **Pedigree Information**

The **m.9185T\>C** variant in MT\-ATP6 has been reported in 34 pedigrees. To date, 118 carriers have been reported. Homoplasmy was reported in 38/118 carriers (32\.2%), and 97/118 carriers (82\.2%) were affected. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (83%), muscle (100%), urine (100%), bone marrow (100%), and fibroblasts (100%) than in hair (35%). The main clinical manifestations among affected carriers included CMT2, ataxia, dHMN phenotype, leigh syndrome, learning disability, peripheral neuropathy, pes cavus, progressive ataxia, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9185 | m.9185T\>C | T9185C\-F1 | China | Mitochondrial ataxia | 0 | 0 | 2018 | [29756269](https://pubmed.ncbi.nlm.nih.gov/29756269/) |  |
| 2 | 9185 | m.9185T\>C |[ T9185C\-F2 ](https://mitofam.com/doc/1815/)| UK | Variable phenotype including Leigh syndrome and NARP\-like disease | 0 | 14 | 2008 | [18461509](https://pubmed.ncbi.nlm.nih.gov/18461509/) |  |
| 3 | 9185 | m.9185T\>C |[ T9185C\-F3](https://mitofam.com/doc/1816) | Canada | Maternally transmitted developmental delay, learning disability and progressive ataxia | 0 | 14 | 2009 | [19626676](https://pubmed.ncbi.nlm.nih.gov/19626676/) | m.9035T\>C co\-occurred with m.4452T\>C; cybrid data supported m.9035T\>C pathogenicity. |
| 4 | 9185 | m.9185T\>C | [T9185C\-F4](https://mitofam.com/doc/1817) | USA | Illness\-induced exacerbation of Leigh syndrome | 2 | 0 | 2010 | [20546952](https://pubmed.ncbi.nlm.nih.gov/20546952/) |  |
| 5 | 9185 | m.9185T\>C | [T9185C\-F5](https://mitofam.com/doc/1818) | France | Leigh syndrome; preimplantation/prenatal diagnosis family | 1 | 0 | 2011 | [21473984](https://pubmed.ncbi.nlm.nih.gov/21473984/) |  |
| 6 | 9185 | m.9185T\>C | [T9185C\-F6 ](https://mitofam.com/doc/1819)| UK | CMT2/dHMN; neuropathy and Leigh\-like disease | 11 | 10 | 2012 | [22933740](https://pubmed.ncbi.nlm.nih.gov/22933740/) | Family A |
| 7 | 9185 | m.9185T\>C | [T9185C\-F7](https://mitofam.com/doc/1820) | UK | CMT2/dHMN | 9 | 8 | 2012 | [22933740](https://pubmed.ncbi.nlm.nih.gov/22933740/) | Family B |
| 8 | 9185 | m.9185T\>C | [T9185C\-F8](https://mitofam.com/doc/1821) | UK | CMT2/dHMN | 11 | 4 | 2012 | [22933740](https://pubmed.ncbi.nlm.nih.gov/22933740/) | Family C |
| 9 | 9185 | m.9185T\>C | T9185C\-F9 | UK | CMT2/dHMN | 7 | 1 | 2012 | [22933740](https://pubmed.ncbi.nlm.nih.gov/22933740/) | Family D |
| 10 | 9185 | m.9185T\>C | T9185C\-F10 | Japan | Leigh\-like syndrome | 0 | 0 | 2017 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 11 | 9185 | m.9185T\>C | [T9185C\-F11](https://mitofam.com/doc/1822) | Poland | Late\-onset Leigh syndrome; hyperventilation | 2 | 1 | 2018 | [29116603](https://pubmed.ncbi.nlm.nih.gov/29116603/) |  |
| 12 | 9185 | m.9185T\>C | T9185C\-F12 | Latvia | Leigh syndrome | 0 | 0 | 2018 | [29228836](https://pubmed.ncbi.nlm.nih.gov/29228836/) |  |
| 13 | 9185 | m.9185T\>C | [T9185C\-F13](https://mitofam.com/doc/1823) | Lithuania | Leigh syndrome | 1 | 0 | 2018 | [29228836](https://pubmed.ncbi.nlm.nih.gov/29228836/) |  |
| 14 | 9185 | m.9185T\>C | T9185C\-F14 | Japan | Early infantile\-onset Leigh syndrome with infantile spasms | 0 | 0 | 2019 | [31500933](https://pubmed.ncbi.nlm.nih.gov/31500933/) | Parents' blood negative by Sanger sequencing. |
| 15 | 9185 | m.9185T\>C | [T9185C\-F15](https://mitofam.com/doc/1824) | Poland | Late\-onset Leigh syndrome; hyperventilation | 1 | 1 | 2018 | [29116603](https://pubmed.ncbi.nlm.nih.gov/29116603/) |  |
| 16 | 9185 | m.9185T\>C |[ T9185C\-F16 ](https://mitofam.com/doc/1825)| UK | Adult\-onset spinocerebellar syndrome | 1 | 4 | 2012 | [22577227](https://pubmed.ncbi.nlm.nih.gov/22577227/) | Family A |
| 17 | 9185 | m.9185T\>C |[ T9185C\-F17](https://mitofam.com/doc/1826) | Canada | Leigh syndrome with ataxia/peripheral neuropathy | 3 | 7 | 2007 | [17352390](https://pubmed.ncbi.nlm.nih.gov/17352390/) |  |
| 18 | 9185 | m.9185T\>C | T9185C\-F18 | France | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 19 | 9185 | m.9185T\>C | T9185C\-F19 | France | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 20 | 9185 | m.9185T\>C | T9185C\-F20 | France | Axonal sensory\-motor peripheral neuropathy; pyramidal syndrome. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 21 | 9185 | m.9185T\>C | T9185C\-F21 | France | Axonal sensory\-motor peripheral neuropathy; mental deficit. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 22 | 9185 | m.9185T\>C | T9185C\-F22 | France | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 23 | 9185 | m.9185T\>C | T9185C\-F23 | France | Axonal sensory\-motor peripheral neuropathy; pyramidal syndrome. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 24 | 9185 | m.9185T\>C | T9185C\-F24 | France | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 25 | 9185 | m.9185T\>C | [T9185C\-F25 ](https://mitofam.com/doc/1827/)| France | Episodic weakness and motor neuropathy; MELAS | 39 | 18 | 2013 | [24153443](https://pubmed.ncbi.nlm.nih.gov/24153443/) |  |
| 26 | 9185 | m.9185T\>C | [T9185C\-F26 ](https://mitofam.com/doc/1828/)| France | Episodic weakness and motor neuropathy | ND | ND | 2013 | [24153443](https://pubmed.ncbi.nlm.nih.gov/24153443/) |  |
| 27 | 9185 | m.9185T\>C | T9185C\-F27 | France | Episodic weakness and motor neuropathy | 0 | 0 | 2013 | [24153443](https://pubmed.ncbi.nlm.nih.gov/24153443/) |  |
| 28 | 9185 | m.9185T\>C | [T9185C\-F28 ](https://mitofam.com/doc/1829/)| Poland | Leigh syndrome / mitochondrial disorder; ptosis and sudden neurological regression | 1 | 0 | 2016 | [27290639](https://pubmed.ncbi.nlm.nih.gov/27290639/) |  |
| 29 | 9185 | m.9185T\>C | T9185C\-F29 | France | Mitochondrial disorder; Leigh syndrome / CNS involvement | 0 | 0 | 2013 | [23847141](https://pubmed.ncbi.nlm.nih.gov/23847141/) |  |
| 30 | 9185 | m.9185T\>C | T9185C\-F30 | France | Mitochondrial disorder; Leigh syndrome / CNS involvement | 0 | 0 | 2013 | [23847141](https://pubmed.ncbi.nlm.nih.gov/23847141/) |  |
| 31 | 9185 | m.9185T\>C | T9185C\-F31 | France | Mitochondrial disorder; adult\-onset ataxia | 0 | 0 | 2013 | [23847141](https://pubmed.ncbi.nlm.nih.gov/23847141/) |  |
| 32 | 9185 | m.9185T\>C | [T9185C\-F32](https://mitofam.com/doc/1830/) | Portugal | Motor neuron syndrome; mitochondrial encephalopathy; Leigh syndrome family history | 0 | 6 | 2014 | [25548692](https://pubmed.ncbi.nlm.nih.gov/25548692/) |  |
| 33 | 9185 | m.9185T\>C |[ T9185C\-F33](https://mitofam.com/doc/1831/) | USA | Episodic weakness; Charcot\-Marie\-Tooth disease type 2 / axonal neuropathy | 0 | 3 | 2016 | [27783406](https://pubmed.ncbi.nlm.nih.gov/27783406/) |  |
| 34 | 9185 | m.9185T\>C | T9185C\-F34 | China | Late\-onset Leigh syndrome | 0 | 0 | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |

# **Carrier Information**

| **No.** | **Position** | **Variant** | **Family ID** | **Carrier ID** | **Type (Fam/De novo/Uninf)** | **Gender (F/M)** | **Proband (Y/N)** | **Affected (Y/N)** | **Die/Alive(D/A)** | **Age** | **Blood Mutant Level** | **Muscle Mutant level** | **Urine Mutant level** | **Other Mutant level** | **Clinical Features** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9185 | m.9185T\>C | T9185C\-F1 | T9185C\-F1\-II2 | Uninf | M | Y | Y | A | 15 | Homo | / | / | / | Mitochondrial ataxia; cognitive impairment; extrapyramidal signs |  |
| 2 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III2 | Fam | ND | Y | Y | A | 24 | Homo | Homo | / | / | Late\-onset Leigh syndrome; gait abnormality; pyramidal signs; weakness; diplopia; dysarthria |  |
| 3 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III6 | Fam | ND | N | Y | D | 7 | Homo | Homo | / | / | Leigh syndrome; failure to thrive; developmental delay; cardiomyopathy; neuropathy; ptosis; bulbar weakness; died |  |
| 4 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III8 | Fam | ND | N | Y | A | 22 | Homo | Homo | / | / | Developmental delay; seizures; ataxia; pyramidal signs; progressive cognitive decline; neuropathy |  |
| 5 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III11 | Fam | ND | N | Y | A | 18 | Homo | / | / | / | Failure to thrive; ataxia; pyramidal signs; neuropathy; progressive cognitive decline |  |
| 6 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III12 | Fam | ND | N | Y | A | 24 | Homo | / | / | / | Foot deformity; learning difficulties; demyelination; Leigh syndrome; progressive leg weakness |  |
| 7 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-II3 | Fam | ND | N | Y | A | 46 | Homo | / | / | / | NARP\-like disease; ataxia; peripheral neuropathy; dysarthria; swallowing difficulty; cognitive decline |  |
| 8 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-II4 | Fam | ND | N | Y | A | 45 | Homo | / | / | / | Falls; distal weakness; demyelinating peripheral neuropathy; dysarthria; ataxia; diplopia; cognitive decline |  |
| 9 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III3 | Fam | ND | N | Y | A | 20 | Homo | / | / | / | Cyclical vomiting; mild ataxia; learning difficulties; neuropathy; dysarthria; diplopia; memory loss |  |
| 10 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III13 | Fam | ND | N | Y | A | 21 | Homo | / | / | / | Failure to thrive; peripheral neuropathy; ataxia; distal weakness and wasting; cognitive decline |  |
| 11 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III1 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Denied symptoms but had pes cavus, absent ankle reflexes and distal wasting |  |
| 12 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III4 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Mild coordination/learning problems with brisk reflexes |  |
| 13 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III5 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Mild coordination/learning problems with brisk reflexes |  |
| 14 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III7 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Mild coordination/learning problems with brisk reflexes |  |
| 15 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III9 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Mild coordination/learning problems with brisk reflexes |  |
| 16 | 9185 | m.9185T\>C | T9185C\-F2 | T9185C\-F2\-III10 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Mild coordination/learning problems with brisk reflexes |  |
| 17 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-II1 | Fam | F | Y | Y | A | 38 | Homo | / | / | / | Thirty\-year dysarthria and ataxia; learning disability; spinocerebellar degeneration |  |
| 18 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-III1 | Fam | F | Y | Y | A | ND | Homo | / | / | / | Developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 19 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-II2 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 20 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-II5 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 21 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-III2 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 22 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-III4 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 23 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-III5 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 24 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-III7 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 25 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-III8 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 26 | 9185 | m.9185T\>C | T9185C\-F3 | T9185C\-F3\-IV1 | Fam | ND | N | Y | A | ND | Homo | / | / | / | Cognitive developmental delay; learning disability; progressive ataxia; sensory neuropathy |  |
| 27 | 9185 | m.9185T\>C | T9185C\-F4 | T9185C\-F4\-IV2 | Fam | M | Y | Y | A | ND | Homo | / | / | / | Leigh syndrome; episodic febrile illness\-induced weakness; endurance intolerance; dysarthria; ataxia; ptosis |  |
| 28 | 9185 | m.9185T\>C | T9185C\-F4 | T9185C\-F4\-III2 | Fam | F | N | N | A | ND | 30% | / | / | / | Healthy |  |
| 29 | 9185 | m.9185T\>C | T9185C\-F5 | T9185C\-F5\-II1 | Fam | F | Y | Y | A | ND | 95% | 95% | 95% | 95%(BM) | Cerebellar ataxia; proximal tubulopathy; basal ganglia and cerebellar MRI lesions; Leigh syndrome |  |
| 30 | 9185 | m.9185T\>C | T9185C\-F5 | T9185C\-F5\-I2 | Uninf | F | N | N | A | ND | 25% | / | 14% | 17%(BM) | Healthy |  |
| 31 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-II1 | Fam | F | N | Y | A | 57 | 100% | / | / | / | Falls; pure motor neuropathy |  |
| 32 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-II3 | Fam | F | N | Y | A | 55 | 100% | / | / | / | Motor neuropathy |  |
| 33 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-II4 | Fam | F | N | N | A | 51 | 63% | / | / | / | Asymptomatic carrier |  |
| 34 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-II5 | Fam | M | N | Y | A | 47 | 100% | / | / | / | Motor neuropathy |  |
| 35 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-III4 | Fam | F | N | Y | A | 32 | 100% | / | / | / | CMT2/dHMN phenotype |  |
| 36 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-III5 | Fam | F | N | Y | D | 16 | 100% | 100% | / | / | Leigh\-like disease; cortical blindness; died |  |
| 37 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-III6 | Fam | M | N | Y | A | 27 | 100% | 100% | / | / | CMT2/dHMN phenotype |  |
| 38 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-III7 | Fam | M | N | Y | A | 25 | 100% | / | 100% | / | CMT2/dHMN phenotype |  |
| 39 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-III8 | Fam | M | Y | Y | A | 21 | 100% | / | / | / | Recurrent falls; foot drop; CMT2/dHMN phenotype |  |
| 40 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-IV1 | Fam | M | N | Y | D | 9 | 100% | / | / | / | Severe neurologic disease; died |  |
| 41 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-IV2 | Fam | F | N | Y | A | 11 | / | 100% | / | / | CMT2/dHMN phenotype |  |
| 42 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-II3 | Fam | F | N | N | A | ND | / | / | / | / | Asymptomatic carrier |  |
| 43 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-II8 | Fam | M | Y | Y | A | 60 | 100% | / | / | / | CMT2/dHMN phenotype |  |
| 44 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-III1 | Fam | F | N | N | A | ND | / | / | / | / | Asymptomatic carrier |  |
| 45 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-III2 | Fam | M | N | Y | A | 49 | 80% | / | / | / | CMT2/dHMN phenotype |  |
| 46 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-III3 | Fam | F | N | Y | A | ND | / | / | / | / | CMT2/dHMN phenotype |  |
| 47 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-III5 | Fam | F | N | N | A | 49 | 73% | / | / | / | Asymptomatic carrier; upper motor neuron signs on examination |  |
| 48 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-III6 | Fam | F | N | Y | A | 46 | 100% | 100% | / | 100%(F) | CMT2/dHMN phenotype |  |
| 49 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-IV3 | Fam | F | N | Y | A | 19 | 100% | / | / | / | CMT2/dHMN phenotype |  |
| 50 | 9185 | m.9185T\>C | T9185C\-F7 | T9185C\-F7\-IV4 | Fam | F | N | N | A | 21 | 39% | / | / | / | Asymptomatic carrier |  |
| 51 | 9185 | m.9185T\>C | T9185C\-F8 | T9185C\-F8\-II4 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 52 | 9185 | m.9185T\>C | T9185C\-F8 | T9185C\-F8\-III5 | Fam | F | N | N | A | 48 | 75% | / | / | / | Asymptomatic carrier |  |
| 53 | 9185 | m.9185T\>C | T9185C\-F8 | T9185C\-F8\-III13 | Fam | M | Y | Y | A | ND | 100% | / | / | / | CMT2/dHMN phenotype |  |
| 54 | 9185 | m.9185T\>C | T9185C\-F8 | T9185C\-F8\-IV1 | Fam | M | N | N | A | 18 | 45% | / | / | / | Asymptomatic carrier |  |
| 55 | 9185 | m.9185T\>C | T9185C\-F8 | T9185C\-F8\-IV2 | Fam | M | N | Y | A | 21 | 100% | / | / | / | CMT2/dHMN phenotype |  |
| 56 | 9185 | m.9185T\>C | T9185C\-F9 | T9185C\-F9\-III1 | Uninf | M | Y | Y | A | 45 | 92% | / | / | / | CMT2/dHMN phenotype |  |
| 57 | 9185 | m.9185T\>C | T9185C\-F10 | T9185C\-F10\-P1 | Fam | ND | Y | Y | A | ND | 80% | / | / | / | Leigh\-like syndrome |  |
| 58 | 9185 | m.9185T\>C | T9185C\-F11 | T9185C\-F11\-F1\-II1 | Fam | F | Y | Y | A | 33 | / | / | / | / | Late\-onset Leigh syndrome; infection\-related respiratory problems; wheelchair dependence after recovery |  |
| 59 | 9185 | m.9185T\>C | T9185C\-F11 | T9185C\-F11\-F1\-III1 | Fam | F | N | Y | A | 5 | / | / | / | / | early speech delay; acute imbalance/ataxia\-like symptoms | daughter of II1 |
| 60 | 9185 | m.9185T\>C | T9185C\-F11 | T9185C\-F11\-F1\-I2 | Fam | F | N | N | A | 61 | 45% | / | 55% | / | Healthy |  |
| 61 | 9185 | m.9185T\>C | T9185C\-F11 | T9185C\-F11\-F1\-II2 | Fam | F | N | N | A | 32 | 15% | / | / | / | Healthy |  |
| 62 | 9185 | m.9185T\>C | T9185C\-F15 | T9185C\-F15\-F2\-II1 | Fam | M | Y | Y | D | 9 | / | / | / | / | Leigh syndrome; acute imbalance, severe weakness and sudden death |  |
| 63 | 9185 | m.9185T\>C | T9185C\-F15 | T9185C\-F15\-F2\-II2 | Fam | M | N | N | A | 18 | \>97% | / | / | / | Healthy |  |
| 64 | 9185 | m.9185T\>C | T9185C\-F15 | T9185C\-F15\-F2\-I2 | Fam | F | N | Y | A | 40 | \>97% | / | \>97% | / | AD diagnosis with atypical dysarthria, swallowing problems, seizures, spasticity and dystonia; LS excluded |  |
| 65 | 9185 | m.9185T\>C | T9185C\-F12 | T9185C\-F12\-P1 | De novo | F | Y | Y | A | 7mo | 95% | / | / | / | Leigh syndrome; refractory seizures; lactic acidosis; neurodegenerative MRI lesions; severe deterioration |  |
| 66 | 9185 | m.9185T\>C | T9185C\-F13 | T9185C\-F13\-II1 | Fam | F | Y | Y | A | 3\.5 | Homo | / | / | / | Leigh syndrome; motor developmental delay; hypotonia; tremor; poor balance; basal ganglia lesions |  |
| 67 | 9185 | m.9185T\>C | T9185C\-F13 | T9185C\-F13\-I2 | Uninf | F | N | N | A | 38 | \+ | \+ | \+ | / | Healthy |  |
| 68 | 9185 | m.9185T\>C | T9185C\-F14 | T9185C\-F14\-P1 | De novo | F | Y | Y | A | 2 | Homo | / | / | / | Early infantile\-onset Leigh syndrome; focal seizures; infantile spasms; profound developmental delay; hypotonic quadriplegia |  |
| 69 | 9185 | m.9185T\>C | T9185C\-F6 | T9185C\-F6\-I1 | Uninf | F | N | ND | A | 80 | 88% | / | / | / | Phenotype unknown in Figure 1; target m.9185T\>C mutant load shown |  |
| 70 | 9185 | m.9185T\>C | T9185C\-F16 | T9185C\-F16\-I1 | Fam | M | Y | Y | A | 58 | / | 98% | / | / | Ataxia; saccade dysmetria; proximal myopathy; cognitive impairment; sensorimotor axonal neuropathy. |  |
| 71 | 9185 | m.9185T\>C | T9185C\-F16 | T9185C\-F16\-I2 | Fam | F | N | Y | A | 55 | 99% | / | / | / | Ataxia; slow extraocular movements; optic pallor; dysarthria; spasticity; dystonia; sensorimotor axonal neuropathy. |  |
| 72 | 9185 | m.9185T\>C | T9185C\-F16 | T9185C\-F16\-I3 | Fam | M | N | Y | A | 51 | 99% | / | / | / | Ataxia; dysarthria; broken ocular pursuit; distal leg atrophy; pyramidal signs; pes cavus; motor axonal neuropathy. |  |
| 73 | 9185 | m.9185T\>C | T9185C\-F16 | T9185C\-F16\-I5 | Fam | F | N | Y | A | 43 | 95% | / | / | / | Ataxia; dysarthria; short stature; distal weakness with foot drop; extensor plantar reflexes; sensorimotor axonal neuropathy. |  |
| 74 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-I1 | Uninf | F | N | N | A | ND | / | / | / | lymphoblast DNA: 52% | Healthy |  |
| 75 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-II2 | Fam | F | N | Y | D | 10 | / | / | / | / | Leigh syndrome; seizures in infancy; encephalitis; weakness; respiratory and renal failure. |  |
| 76 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-II3 | Fam | F | N | Y | A | ND | / | / | / | lymphoblast DNA: 86% | Ataxia and weakness; Charcot\-Marie\-Tooth disease with ataxia. |  |
| 77 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-II4 | Fam | F | N | N | A | ND | / | / | / | lymphoblast DNA: 81% | Healthy |  |
| 78 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-II5 | Fam | F | N | Y | D | ND | / | / | / | / | Leigh syndrome. |  |
| 79 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-II7 | Fam | M | N | Y | A | 3 | / | / | / | lymphoblast DNA: 85% | Peripheral neuropathy/ataxia; poor gait onset 3; hypotonic ankle weakness; diminished joint position and vibration sense. |  |
| 80 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-III4 | Fam | F | N | Y | A | 10 | / | / | / | lymphoblast DNA: 90% | Intermittent acute ataxia; muscle weakness; ptosis. |  |
| 81 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-III5 | Fam | M | N | Y | A | 7 | / | / | / | lymphoblast DNA: 91% | Lassitude; partial ptosis; ataxia. |  |
| 82 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-III6 | Fam | M | N | N | A | ND | / | / | / | lymphoblast DNA: 17% | Healthy |  |
| 83 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-III7 | Fam | M | Y | Y | A | 8\.5 | \>90% | / | / | skin fibroblasts and lymphocytes: \>90%; lymphoblast DNA: 90% | Leigh syndrome; ataxia; frequent falls; slowed speech; basal ganglia lesions. |  |
| 84 | 9185 | m.9185T\>C | T9185C\-F17 | T9185C\-F17\-III8 | Fam | M | N | Y | A | 7 | \>90% | / | / | skin fibroblasts and lymphocytes: \>90%; lymphoblast DNA: 91% | Leigh syndrome/ataxia after viral illness; cerebellar MRI abnormality. |  |
| 85 | 9185 | m.9185T\>C | T9185C\-F18 | T9185C\-F18\-P1 | Uninf | ND | Y | Y | A | 37 | 100% | / | 100% | / | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. |  |
| 86 | 9185 | m.9185T\>C | T9185C\-F19 | T9185C\-F19\-P1 | Uninf | ND | Y | Y | A | 31 | 100% | / | / | / | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. |  |
| 87 | 9185 | m.9185T\>C | T9185C\-F20 | T9185C\-F20\-P1 | Uninf | ND | Y | Y | D | 51 | / | 100% | / | / | Axonal sensory\-motor peripheral neuropathy; pyramidal syndrome. |  |
| 88 | 9185 | m.9185T\>C | T9185C\-F21 | T9185C\-F21\-P1 | Uninf | ND | Y | Y | A | 15 | 100% | / | / | / | Axonal sensory\-motor peripheral neuropathy; mental deficit. |  |
| 89 | 9185 | m.9185T\>C | T9185C\-F22 | T9185C\-F22\-P1 | Uninf | ND | Y | Y | A | 25 | 100% | / | / | / | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. |  |
| 90 | 9185 | m.9185T\>C | T9185C\-F23 | T9185C\-F23\-P1 | Uninf | ND | Y | Y | A | 35 | 100% | / | / | / | Axonal sensory\-motor peripheral neuropathy; pyramidal syndrome. |  |
| 91 | 9185 | m.9185T\>C | T9185C\-F24 | T9185C\-F24\-P1 | Uninf | ND | Y | Y | A | 30 | 90% | / | / | / | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. |  |
| 92 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-III6 | Fam | F | N | Y | A | 60 | 83% | 100% | 100% | 100%(BM); 35%(H); 100%(F) | Gait disturbance. |  |
| 93 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-IV2 | Fam | F | N | Y | A | ND | 100% | / | 74% | 95%(BM); 77%(H) | peripheral neuropathy |  |
| 94 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-IV3 | Fam | F | N | Y | A | ND | 53% | / | 94% | 85%(BM); 81%(H) | peripheral neuropathy |  |
| 95 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-IV4 | Fam | M | N | Y | A | ND | 100% | / | 98% | 99%(BM); 98%(H) | peripheral neuropathy |  |
| 96 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-IV5 | Fam | F | N | Y | A | 43 | 98% | 100% | 78% | 100%(BM); 100%(H); 99%(F) | Periodic paralysis onset 18 y; diplopia onset 36 y; gait disorder onset 33 y; pes cavus; proprioceptive ataxia; pyramidal syndrome; motor neuropathy UL\+LL. | Carrying m.3271T\>C |
| 97 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-IV6 | Fam | F | N | N | A | ND | 87% | / | 74% | 67%(BM); 67%(H) | Healthy |  |
| 98 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-IV16 | Fam | M | N | Y | A | ND | 99% | / | 89% | 99%(BM); 97%(H) | peripheral neuropathy |  |
| 99 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-V3 | Fam | M | N | Y | A | ND | 100% | / | 100% | 100%(BM); 78%(H) | peripheral neuropathy |  |
| 100 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-V5 | Fam | F | N | Y | A | ND | 89% | / | 99% | 100%(BM); 100%(H); 99%(F) | Periodic paralysis onset 13 y; diplopia onset 21 y; gait disorder since childhood; pes cavus; proprioceptive and cerebellar ataxia; pyramidal syndrome; cognitive impairment; motor neuropathy UL\+LL. |  |
| 101 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-V9 | Fam | F | Y | Y | D | 15 | 82% | 100% | 94% | 98%(BM); 92%(H) | Typical MELAS syndrome | Carrying m.3271T\>C |
| 102 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-V12 | Fam | F | N | Y | A | 24 | 99% | 98% | / | 88%(BM); 96%(H) | Periodic paralysis onset 12 y; diplopia onset 25 y; gait disorder onset 18 y; pes cavus; proprioceptive ataxia; motor neuropathy UL\+LL; brain MRI normal. |  |
| 103 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-V13 | Fam | F | N | Y | A | ND | / | / | / | 99%(BM); 99%(H) | peripheral neuropathy |  |
| 104 | 9185 | m.9185T\>C | T9185C\-F25 | T9185C\-F25\-V18 | Fam | F | N | ND | A | ND | 73% | / | 71% | / | pes cavus |  |
| 105 | 9185 | m.9185T\>C | T9185C\-F26 | T9185C\-F26\-P1 | Uninf | F | ND | Y | ND | ND | Homo | / | / | / | Periodic paralysis; gait disorder; pes cavus; motor neuropathy LL. |  |
| 106 | 9185 | m.9185T\>C | T9185C\-F26 | T9185C\-F26\-P2 | Uninf | M | ND | Y | ND | ND | Homo | / | / | / | Periodic paralysis; gait disorder; pes cavus; motor neuropathy LL. |  |
| 107 | 9185 | m.9185T\>C | T9185C\-F27 | T9185C\-F27\-P1 | Uninf | M | Y | Y | ND | ND | Homo | / | / | / | Periodic paralysis; gait disorder; pes cavus; pyramidal syndrome; motor neuropathy LL. |  |
| 108 | 9185 | m.9185T\>C | T9185C\-F28 | T9185C\-F28\-II1 | Fam | M | Y | Y | D | 9 y | Homo | / | / | / | Ptosis; sudden neurological regression; typical Leigh syndrome changes on brain autopsy |  |
| 109 | 9185 | m.9185T\>C | T9185C\-F28 | T9185C\-F28\-I2 | Uninf | F | N | Y | A | ND | \+ | / | / | / | PSEN1\-related early Alzheimer disease | Carrying PSEN1 |
| 110 | 9185 | m.9185T\>C | T9185C\-F28 | T9185C\-F28\-II2 | Fam | M | N | N | A | ND | \+ | / | / | / | Healthy |  |
| 111 | 9185 | m.9185T\>C | T9185C\-F29 | T9185C\-F29\-P1 | Uninf | F | Y | Y | ND | 1\-16 onset | / | / | / | Heteroplasmic(tissue NR; load NR) | CNS involvement with psychomotor regression and ataxia; renal involvement; intrauterine/postnatal growth failure; anaemia; Leigh MRI; increased blood lactate; lipidosis/RRF; complex V deficiency in muscle. |  |
| 112 | 9185 | m.9185T\>C | T9185C\-F30 | T9185C\-F30\-P1 | Uninf | M | Y | Y | ND | 1\-16 onset | / | / | / | Heteroplasmic(tissue NR; load NR) | CNS involvement with psychomotor regression and ataxia; peripheral neuropathy; Leigh/cerebellar atrophy MRI; increased CSF lactate; normal muscle histology and respiratory chain in muscle/fibroblasts. |  |
| 113 | 9185 | m.9185T\>C | T9185C\-F31 | T9185C\-F31\-P1 | Uninf | F | Y | Y | ND | \>16 onset | / | / | / | Homo(tissue NR) | CNS ataxia; table\-only homoplasmic MitoChip case; normal muscle histology and normal respiratory chain in muscle. |  |
| 114 | 9185 | m.9185T\>C | T9185C\-F32 | T9185C\-F32\-II4 | Fam | M | Y | Y | A | 33 | / | / | / | Homo(tissue NR) | Cognitive impairment; exercise intolerance; progressive muscle weakness; global hypotonia; proximal tetraparesis; chronic neurogenic EMG; muscle biopsy suggestive of SMA/mitochondriopathy; elevated lactate. |  |
| 115 | 9185 | m.9185T\>C | T9185C\-F32 | T9185C\-F32\-II5 | Fam | F | N | Y | A | 22 | / | / | / | Homo(tissue NR) | Mild cognitive impairment; ataxia; exercise intolerance; pes cavus; hammertoes; proximal muscle weakness; axonal peripheral neuropathy; cerebellar atrophy. |  |
| 116 | 9185 | m.9185T\>C | T9185C\-F33 | T9185C\-F33\-I2 | Uninf | F | Y | Y | A | 64 | / | / | / | Homo(tissue NR) | CMT2/chronic distal axonal polyneuropathy; pes cavus/hammertoes; episodic weakness responsive to acetazolamide; sensory ataxia; progressive lower\-limb weakness; wheelchair use most of the time. |  |
| 117 | 9185 | m.9185T\>C | T9185C\-F33 | T9185C\-F33\-II1 | Fam | F | N | Y | A | 34 | / | / | / | Homo(tissue NR) | episodic weakness from age 18; sensorimotor axonal polyneuropathy; distal lower\-limb weakness; foot muscle atrophy; pes cavus; acetazolamide response. |  |
| 118 | 9185 | m.9185T\>C | T9185C\-F34 | T9185C\-F34\-P1 | Uninf | F | Y | Y | ND | 8 onset | 98% | / | / | / | Late\-onset Leigh syndrome; ataxia; pyramidal signs. |  |

For abbreviations and other usage instructions, please see [Mitofam Info](https://mitofam.com/doc/385/).